Assessment of postoperative adjuvant treatment using toceranib phosphate against adenocarcinoma in dogs

Abstract Background Toceranib phosphate (TOC) could be made widely available for treating tumors in dogs if evidence shows that TOC inhibits recurrence after surgery. Objectives To investigate how postoperative adjuvant treatment with TOC modulates the tumor microenvironment (TME), by assessing effects on angiogenic activity, tumor‐infiltrating regulatory T cells (Tregs), and intratumoral hypoxia. Animals Ninety‐two client‐owned dogs were included: 28 with apocrine gland anal sac adenocarcinoma, 24 with small intestinal adenocarcinoma, 22 with lung adenocarcinoma, and 18 with renal cell carcinoma. Methods Retrospective, multicenter study comparing time to progression (TTP) between 42 dogs treated by surgery and TOC and 50 dogs treated by surgery alone. Differences were analyzed in the expression of vascular endothelial growth factor receptor‐2 (VEGFR2) and the number of Foxp3+ Tregs and hypoxia‐inducible factor (HIF)‐1α+ cells in tumor tissues sampled at the first and second (recurrence) surgeries. Results Median TTP for dogs treated by surgery and TOC (360 days) was higher than that for dogs treated by surgery alone (298 days; hazard ratio, 0.82; 95% confidence interval [CI], 0.65‐0.96; P = .02). In dogs treated by surgery and TOC, VEGFR2 expression and the number of Tregs and HIF‐1α+ cells were significantly lower in tissues sampled at the second surgery than in those sampled after the first surgery. In dogs treated by surgery alone, significant differences were found between samples from the 2 surgeries. Conclusions and Clinical Importance Toceranib phosphate could prove to be a useful postoperative adjuvant treatment because of its modulation of the TME.